NM_000136.3(FANCC):c.1582C>T (p.Gln528Ter) AND Fanconi anemia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 28, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003523908.2

Allele description [Variation Report for NM_000136.3(FANCC):c.1582C>T (p.Gln528Ter)]

NM_000136.3(FANCC):c.1582C>T (p.Gln528Ter)

Genes:

FANCC:FA complementation group C [Gene - OMIM - HGNC]
AOPEP:aminopeptidase O (putative) [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9q22.32

Genomic location:

Preferred name:

NM_000136.3(FANCC):c.1582C>T (p.Gln528Ter)

HGVS:

NC_000009.12:g.95101802G>A
NG_011707.1:g.220908C>T
NG_027833.2:g.380105G>A
NG_116860.1:g.244G>A
NM_000136.3:c.1582C>TMANE SELECT
NM_001243743.2:c.1582C>T
NP_000127.2:p.Gln528Ter
NP_000127.2:p.Gln528Ter
NP_001230672.1:p.Gln528Ter
LRG_497t1:c.1582C>T
LRG_497:g.220908C>T
LRG_497p1:p.Gln528Ter
NC_000009.11:g.97864084G>A
NM_000136.2:c.1582C>T

Protein change:

Q528*

Molecular consequence:

NM_000136.3:c.1582C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001243743.2:c.1582C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Fanconi anemia (FA)
Synonyms:: Fanconi pancytopenia; Fanconi's anemia
Identifiers:: MONDO: MONDO:0019391; MeSH: D005199; MedGen: C0015625; Orphanet: 84; OMIM: PS227650

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004253999	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 28, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 8703809, 11050007, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004253999

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 28, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Positive diepoxybutane test in only one of two brothers found to be compound heterozygotes for Fanconi's anaemia complementation group C mutations.

Dokal I, Chase A, Morgan NV, Coulthard S, Hall G, Mathew CG, Roberts I.

Br J Haematol. 1996 Jun;93(4):813-6.

PubMed [citation]

PMID:: 8703809

The fanconi anemia proteins FANCA and FANCG stabilize each other and promote the nuclear accumulation of the Fanconi anemia complex.

Garcia-Higuera I, Kuang Y, Denham J, D'Andrea AD.

Blood. 2000 Nov 1;96(9):3224-30.

PubMed [citation]

PMID:: 11050007

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004253999.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Gln528*) in the FANCC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 31 amino acid(s) of the FANCC protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with FANCC-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant disrupts a region of the FANCC protein in which other variant(s) (p.Leu554Pro) have been determined to be pathogenic (PMID: 8703809, 11050007). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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